Hormonal Contraceptives:
Good, Bad and Controversial
Herbert L. Muncie, Jr., M.D.
Susie


15 year old female comes in to discuss
contraception
She is healthy but wanted to talk about
starting birth control pills


What questions need to be asked?
What issues need to be addressed before
considering hormonal contraception
Oral contraceptives (OCPs)


Approximately 80% of women will use
OCPs during their lifetime
Success rate if instructions followed
perfectly - 99.9% first year of use


Any missed pills - success rate 95%
Adolescent’s success rate - 85-90%
OCPs - Estrogens

Two in U.S.  Ethinyl estradiol (EE)
 Mestranol - 50 µg converted to 40 µg
of EE
OCPs - Progesterones
Progesterone
Classification
Family
• Ethynodiol diacetate 1st Generation
• Norethindrone
• Norethindrone
acetate
• Levonorgestrel (LNg) 2nd Generation
• Norgestrel
Estrane
(short ½ life)
• Desogestrel
• Norgestimate
Gonane
3rd Generation
Gonane
(longer ½ life)
Progestins (family) & OCPs
Examples
Demulen® 1/35
Ethynodiol diacetate
Norinyl® 1/35, Ovcon®35, Ortho
Novum 1/35®
Loestrin®
Norethindrone
Alesse®, Lybrel®, Seasonale®,
Triphasil®, Tri-Levlen®
Ovral®, Lo-Ovral®
Levonorgestrel
Desogen®, Mircette®, Ortho-Cept®
Desogestrel
Ortho-Cyclen®, Ortho Tri-Cyclen®
Norgestimate
Norethindrone acetate
Norgestrel
Mechanisms of action

Estrogen component


Inhibits ovulation by suppressing FSH & LH
Alters secretions & cellular structure of
endometrial lining

Prevents implantation
Mechanisms of action

Progesterone component



Inhibits ovulation by suppressing LH
Thickens cervical mucous & impairs sperm
transport
Alters endometrial lining

Prevents implantation
Dosage and formulations

EE always ≤ 50 µg




20 μg pill in randomized trial had reduced
breast tenderness and bloating
20 mcg pills have higher failure rate with
missed pills (Medical Letter Treatment Guidelines 2007)
10 mcg pill approved (Lo-Lo-Estrin®)
Progestin ≤ 1 mg

Primarily responsible for contraceptive
efficacy
OCP - Yasmin®, Yaz®

First with progestin – drospirenone 3 mg



Analog spironolactone
Avoid in renal insufficiency, hepatic dysfunction
or adrenal insufficiency
Manufacturer recommends measuring K+
during 1st cycle in women regularly taking drugs
that may increase K+ (ACE, ARB or NSAID)

Studies examining hyperkalemia & associated
arrhythmias have not found higher rates
including women taking K+ sparing drugs
OCP - Yasmin®, Yaz®




Equivalent benefit with acne
Improves hirsutism & lowers BP
Initial weight loss followed by gradual
weight return
Thromboembolism has been reported
Audience Question
18 year old female with mild acne wants to start
OCP for contraception. Normal physical, no prior
OCP use. Periods variable from 26 – 45 days.
For this patient I would prescribe a:
a)
b)
c)
d)
Monophasic pill
Biphasic pill
Triphasic pill
Nonhormonal contraception method
Monophasic pills

Estrogen

Progesterone
Day 1
Day 21
Biphasic pill (Necon )
®

Estrogen

Progesterone
Day 11
Triphasic pills

Estrogen

Progesterone
Day 8
Examples – Caziant®; Cylessa®; Necon 7/7/7®; OrthoNovum 7/7/7 ®; Ortho Tri-Cyclen ®; Tri-Sprintec®;
TriNessa®; Velivet®
Day15
Triphasic pills


Estrogen
Progesterone
Ex. Tri-Norinyl®; Aranell®; Leena®
Day 8
Ex. Estrostep
Fe®; TriLegest
Fe®; Tilia Fe®
Day 6
Day 17
Ex. TriNessa®; TriVora®; Enpresse®
Day 7
Day 12
Day 13
Four-phase pill
(Natazia®) estradiol valerate/dienogest 3 mg/0 mg x2, then
2 mg/2 mg x5, then 2 mg/3 mg x17, then 1 mg/0 mg x2

Estrogen

Progesterone
Day 3
Day 8
Day 25
Day 27
Monophasic, Biphasic or
Triphasic?

Biphasic & triphasic pills were developed to
reduce side effects of monophasic pills

Biphasic with norethindrone associated with inferior
cycle control compared to triphasic with
levonorgestrel [Cochrane Review 2005]


Progestin may be more important than phasic type
Monophasic pills give better cycle control

Triphasic pills offer no physiologic advantage

No data to support triphasic over monophasic pills
OCP general benefits





Decreased
dysmenorrhea
Reduced menstrual
flow
Reduced risk of
anemia
Improves acne
Eliminate
mittelschmerz





Decreased risk of
ectopic pregnancy
Decreased risk of PID
Decreased sxs of PMS
Improvement in
endometriosis
Suppression of ovarian
& breast cyst formation
OCP – Benefit

Endometrial cancer reduced




50% reduction if used in prior 12 months
Maximum protection if use continues for
3 years
Protection lasts for 15 + years
High or low dose pills provide protection
OCP – Benefit

Ovarian cancer reduced

40% reduction in risk over nonusers


Begins after 3-6 months of use


High dose or low dose pills - same benefit
80% reduction after 10 years of use
Reduced risk with family history ovarian
CA & 4-8 yrs. use
OCP Cardiovascular Risks


Increased risk of CVD in smokers over
age 35
Small increased risk MI with 2nd
generation progesterones


Only with current users – no lingering effect
Slight increased risk of ischemic stroke

2-6 fold increase of ischemic stroke with
history of classic migraine
OCP - Risks

Headaches

May increase or decrease


If HA persists with normal BP & no focal deficit


Headaches attributed to initiation of OCP tend
to improve over time
Lower dosage of estrogen, progestin or both
(no evidence effective)
If HA persists with increased BP or focal deficit

Discontinue OCP
OCP - Risks

OCP use associated with increased risk
of developing systemic lupus
erythematosus (SLE)

Especially if started recently [Bernier 2009]

However, very low risk overall
VTE Risk

VTE Risk


3-6 fold increased risk VTE, highest first 6-12
months of use (SOR B)
Older women have greater risk



> age 39 100/100,000 person-years
Adolescents - 25/100,000 person-years
Obesity doubles the risk
VTE Risks

VTE Risk


Risk decreases with longer duration of use
For same estrogen dose - desogestrel &
drospirenone have significantly higher risk
[Lidegaard 2009]

Grapefruit juice can augment bioavailability of
EE [Grande LA 2009]
OCP Risks - EBM

Risks (SOR B)


Increase in cervical cancer after 8 or more
years of use after adjusting for HPV infection
Risk of CIN 2 - 3 with oncogenic HPV


Decreased with depot-medroxyprogesterone
(DMPA - Depo-Provera®)
No association with combination OCPs
[Harris 2009]
OCP Risks/Benefits - EBM

No increased risk of weight gain (SOR A)

Weight gain does occur with DMPA – 5.1 kg
No increased risk breast cancer (SOR B)
 No consistent change in breast milk
production (SOR A)



Or in infant growth or weight (SOR B)
Women who use OCP are not at an
increased risk of death later in life

In fact a net benefit was found
OCPs can be used with these
conditions




Diabetes mellitus
< 35 years old
Nonsmoker > age 35
Smokers < 35 years
old
Obese women

Caution > age 39




Controlled hypertensive
Ulcerative colitis
Pituitary adenomas
After gestational
diabetes
OCPs and Stable SLE - EBM

OCPs are safe & do not increase the risk
of flares in women with stable SLE

InfoRetriever

Randomized controlled trial (double-blinded)

Level of Evidence (LOE) 1 b

http://www.infopeoms.com/irsearch/search_details.cfm?ID=802
05&ResultKey=E&title=OCPs%20safe%20in%20women%20wi
th%20SLE
OCP Contraindications


History of DVT, PE or arterial clotting
Family history clotting or thrombotic events
 Family history (FH) if positive is risk factor VTE

Ask if parent or sibling ever had VTE


Positive FH if 1 relative was < 50 yo when VTE
occurred
Positive FH if 2 or more relatives at any age had
VTE [Bezemer 2009]
OCP Contraindications




Smoking and ≥ 35 years old
Uncontrolled hypertension
Migraine with aura
Undiagnosed genital bleeding
OCP Contraindications


Pregnancy – not harmful, just too late
Sickle cell (SS) or sickle C (SC) disease
not absolutely contraindicated

DMPA may be preferable for SS disease
Duration of Use

Non-smokers – OCPs can be used into
menopause

To determine if menopausal d/c OCP & obtain
FSH one month later




If FSH > 40 ng/mL = menopausal
Not proven reliable indicator, alternative just
stop in early to mid 50s
Smokers – stop at age 35
If treating vasomotor symptoms consider
continuous active pills
Drug Interactions

Vitamin C

Increases estrogen level


Discontinuation of vitamin C may precipitate
bleeding


Can induce nausea
Decreased estrogen level
Antibiotics

Unclear impact on efficacy
Drug Interactions

Anticonvulsants

Advise patients to use a different form of
contraception


Because some anticonvulsants may reduce
efficacy of OCPs
If you & patient decide to use OCP, use pill
with 50 µg EE


If breakthrough bleeding occurs with that pill
Patient should use alternative contraceptive
method
Frequency of menstruation

Before initiating OCPs ask how often
the patient wants to menstruate



Monthly? (Every 4 weeks)
Quarterly? (Every 91 days)
Never?
Rarely Menstruate

Seasonale® (2004)
84 days active pills with levonorgestrel (0.15 mg)
& EE (30 mcg)
 7 days placebo
 Increased risk unsuspected bleeding first
6 months of use

Never Menstruate

Lybrel® approved in 2007 for continuous use


365 days active pills
EE 20 mcg & levonorgestrel 0.09 mg every day
Continuous OCPs


Women who use a continuous combination OCP
will have less bleeding without an increase in
adverse effects
Reduced frequency of hormone withdrawal side
effects

Reduced headache, pelvic pain, bloating, breast
tenderness
Susie


15 year old female who came in to discuss
contraception
Questions that were asked



Family history negative for VTE or cancer
Wants to menstruate monthly
Given prescription for generic monophasic
pill and she was told to start the pills today

Had a negative pregnancy test in the office
OCP formulations
OCP
Active
Placebo Low dose
active
Standard
21
7
0
Mircette®
21
2
5
Seasonique®
84
0
7
Loestrin® 24 Fe
24
4
0
Yaz® (20 mcg EE)
24
4
0
Femcon® Fe (chewable
pill)
Natazia™
21
7
0
26
2
0
Question
51%
29%
You are starting for the first
time OCPs with a 19
yo patient. No previous OCP use. Normal family
history & physical exam. When 11%
will you advise
9%
her to take the first pill
of the first pack?
...
...
ee
y
da
y
Is
da
Th
e
st
fir
Th
e
st
fir
Th
e
Su
nd
a
y
Su
n
af
t..
.
d.
..
The Sunday after her next period starts
The first Sunday after next period ends
The first day of her next period
The day I see her in the office
Th
e
a)
b)
c)
d)
Starting OCPs – 3 Options
1. “Sunday start” – take the 1st pill of the
1st pack the 1st Sunday after onset of
menses



Reduces menses on weekend
May not suppress ovulation with first cycle
Advise additional contraception 1st month
Starting OCPs – 3 Options
2. “First-day start” - take the 1st pill of the
1st pack the 1st day of next menses



Easier to remember & explain
Immediately protective as birth control
Less breakthrough bleeding
Starting OCPs – 3 Options
3. “Visit day start” - take the 1st pill of the 1st
pack the day of the visit

“Quick start” - watch patient take 1st pill



Negative pregnancy test & no intercourse prior 2
weeks, no immediate follow-up
If intercourse within prior 2 weeks, repeat
pregnancy test in 2 weeks
Additional contraception the first 7 days
Quick-Start contraception

Main benefit is reduced time explaining how
to start pills [Westhoff 2007]


No evidence reduced risk of pregnancy or
discontinuation rates for OCPs [Cochrane 2008]
Fewer women on quick-start Depo-Provera
became pregnant than women who started
another method [Lopez 2008]
The Prescription
Dr. Understanding
Sarasota, Fl
Dr. Understanding
Sarasota, Fl
Jane Smith
Jane Smith
Sig: 3 OCP Packs
Sig: 1 OCP Packs
Refill: x 3
Refill: x 12
Better Option?
Dr. Understanding
Sarasota, Fl

Dispensing 13 cycles at a
single visit lead to better
continuation rates &
decreased cost [Foster 2006]

Women who received 13
cycles were more likely to
have PAP testing &
chlamydia screening
Jane Smith
Sig: 13 OCP Packs
Refill: x 0
Audience Question
How often are pills forgotten?
During a three month period, how many pills
does the average woman miss each cycle?
a)
b)
c)
d)
e)
1.2
2.6
3.5
4.1
4.9
Missing pill instructions

First ask which pill(s) were missed:


If active pill and < 24 hrs late


If placebo pill just skip it
Take immediately
If active pill and ≥ 24 but < 48 hrs late


Take both pills at the same time
Additional contraception not required
Missing pill instructions

If 2 active pills missed




Double up for 2 days
Use additional contraceptive method for 7 days
Consider emergency contraception if unprotected
intercourse
If ≥ 3 active pills missed




Stop pills and begin new pack
Use additional contraceptive method for 7 days
Consider emergency contraception if unprotected
intercourse
Discuss alternative contraceptive options that do not
require daily compliance
Most Dangerous pill to Miss?

Most dangerous pill to miss is
the 1st pill of the new pack

Pill free > 7 days increases risk
ovulation


Use additional form of birth
control until taken 7
consecutive active pills
Stress compliance with starting
each new pack
Audience Question
26 y.o. patient at her 6 weeks postpartum visit
requests contraception. Exclusively breastfeeding.
Used combination OCP is the past. Which
contraceptive option would you recommend?
a)
b)
c)
d)
Progesterone IUD
Low-dose combination OCP
Progesterone only OCP
Continue exclusively breastfeeding and return
for contraception at 6 months or when
supplementing with formula
Progestin only pills

Thicken cervical mucous & prevent sperm
ascending through os



Irregular bleeding more common
Daily compliance crucial


Erratic suppression ovulation
Same time every day (2-3 hr difference can
cause bleeding, allow ovulation)
Are not contraindicated in smokers over
age 35
OCP - Postpartum

Can begin combination OCP ≥ 3 weeks
postpartum after delivery ≥ 20 weeks
gestation



Starting < 3 weeks postpartum associated
with increased risk of VTE
Balance this against risk of unwanted
pregnancy which has greater risk of VTE
For delivery of < 20 weeks gestation can begin combination OCP immediately
OCP – Breast feeding

Can start combination OCP at 6 weeks
post-partum if lactation is well established
and other forms of contraception are not
acceptable [ACOG Position Statement 2004]
Audience Question
26 y.o. patient at her 6 weeks postpartum visit
requests contraception. Exclusively breastfeeding.
Used combination OCP is the past. Which
contraceptive option would you recommend?
a)
b)
c)
d)
Progesterone IUD
Low-dose combination OCP
Progesterone only OCP
Continue exclusively breastfeeding and return
for contraception at 6 months or when
supplementing with formula
Progestin only pills

Thicken cervical mucous & prevent sperm
ascending through os



Irregular bleeding more common
Daily compliance crucial


Erratic suppression ovulation
Same time every day (2-3 hr difference can
cause bleeding, allow ovulation)
Are not contraindicated in smokers over
age 35
OCP - Postpartum

Can begin combination OCP ≥ 3 weeks
postpartum after delivery ≥ 20 weeks
gestation



Starting < 3 weeks postpartum associated
with increased risk of VTE
Balance this against risk of unwanted
pregnancy which has greater risk of VTE
For delivery of < 20 weeks gestation can begin combination OCP immediately
OCP – Breast feeding

Can start combination OCP at 6 weeks
post-partum if lactation is well established
and other forms of contraception are not
acceptable [ACOG Position Statement 2004]
Hormonal Contraception Other than Oral
Contraceptive Patch

Ortho Evra® (EE 20 mcg; norelgestromin
150 mcg/day)
 Apply abdomen, buttocks upper torso
(exclude breast) or upper outer arm
th week
 One patch a week for 3 weeks, 4
patch free
Contraceptive Patch

Equally efficacious to OCP

Side effects



Breast discomfort, headache, nausea & cramps
– perhaps more than with OCP
Less effective - women > 90 kg
FDA warning of higher hormone levels than
previously reported – may increase risk of VTE
Hormonal vaginal ring

NuvaRing® - EE15 mcg & etonogestrel 12
mcg/day

One ring for three weeks



No ring for one week
If ring is out > 3 hours use additional
contraception until ring in place for 7 days
Does not have to be in specific position

Hormones absorbed anywhere in vagina
Hormonal vaginal ring

NuvaRing®


Contraceptive hormone levels for 35 days
Alternative regimen



One ring a month
Same day of the month (e.g. 12th of every month)
Reduces number of menses & hormonal
withdrawal side effects [Sulak 2008]
Patch & Ring – EBM

Cochrane review found:


Patch caused more side effects than OCP
Ring caused fewer side effects than OCP

Except vaginal discharge & vaginitis
Obese women - EBM

What hormonal contraception is most
effective?


Depo-Provera & NuvaRing® are not affected by
body weight (SOR B)
Obese women using oral contraceptives have
increased risk of pregnancy (SOR B)
[Clinical Inquiries 2007]

However, new evidence found ovarian
suppression was the same for obese women
who were consistent users of OCP
Contraceptive Failure Rate
Method
No method
Diaphragm with spermicide
Condom – male
OCPs
Transdermal
Transvaginal
Injectable
IUD – copper
IUD – progesterone
Implant
Typical Use
85%
16%
15%
8%
8%
8%
3%
0.8%
0.2%
0.05%
Perfect Use
85%
6%
2%
0.3%
0.3%
0.3%
0.3%
0.6%
0.2%
0.05%
Emergency Contraception (EC)

Woman at risk for unwanted pregnancy







Condom broke or slipped
Forced intercourse
Intercourse and no method of BC
Diaphragm or cervical cap dislodged
Two or more OCPs missed or forgotten
> 12 weeks from last depo progesterone
injection
Missed first pill of OCP
Emergency Contraception

Woman at risk for unwanted pregnancy
 Contraceptive patch (Ortho Evra®)




Off > 24 hours during active week
Left on > 9 days
> 2 days late putting on active week patch
NuvaRing®



Taken out > 3 hours during active weeks
Left in > 5 weeks in a row
> 2 days late inserting new ring
Emergency Contraception

Mechanism of action 



Inhibits or delays ovulation if prior to ovulation
Interferes with egg/sperm transport
Alters endometrium and prevents implantation
Does not terminate established pregnancy



ACOG - only contraindication is pregnancy
 Because it doesn’t work
History of ectopic pregnancy not contraindication
 Careful follow-up since higher risk of repeat ectopic
Smoking & over age 35 not contraindication
Emergency Contraception

Progestin only (Plan B®)


0.75 mg levonorgestrel – two doses 12
hours apart
Single 1.5 mg pill available (Plan B One Step®)
Emergency Contraception

Fewer side effects & better efficacy





95% within 24 hrs, 85% within 25-48 hr
Can be used up to 5 days after intercourse
No clinical exam or pregnancy test is
necessary before EC
EC may be used again even if used before
within the same menstrual cycle
Available OTC for women ≥ 17 yo
Emergency Contraception

Ulipristal (Ella®) approved for EC




Selective progesterone receptor modulator
(SPRM) – 30 mg single dose
Remains equally effective up to five day after
unprotected intercourse
Possibility it is less effective in women with
BMI > 30
Requires a prescription

No significant side effects but long-term data
is not yet available
Emergency Contraception

Follow-up care

Document patient has normal menses within
21 days

Obtain B-hCG level if no menses in 21 days

Discuss starting ongoing contraception at the
start of induced menses
Key Points Hormonal Contraception

No one OCP has any unique advantage

Become comfortable with 4 formulations that allow
adjustment in estrogen & progesterone dosage

Weigh risks vs. benefits before initiating hormonal
contraception

Compliance may be enhanced with alternative
delivery system (patch, ring)

Discuss availability of emergency contraception
What Questions do
you have?